Halogenated anilides of thiophene carboxylic acids



United States Patent 3,303,201 HALOGENATED ANILIDES OF THIOPHENE CARBOXYLIC ACIDS Herbert C. Stecker, 1 Bridle Way, Ho-Ho-Kus, NJ. 07423 No Drawing. Filed Sept. 30, 1965, Set. N0. 491,901 3 Claims. (Cl. 260332.2)

This application is continuation-in-part of copending application Serial No. 347,007, filed on February 24, 1964, by Herbert C. Stecker now matured to US. Pat. No. 3,243,342.

This invention deals with halogenated anilides of thiophene carboxylic acids. More specifically, it relates to compounds having the following generic formula:

AH III wherein X is chlorine, bromine, or iodine, X is chlorine, bromide, iodine, or trifluorornethyl, A is oxygen or sulfur, a is a numeralfrom 0 to 2, and b is a numeral from 1 to 3.

The compounds of the present invention may be prepared in accordance with the method outlined 'by Hopper, MacGregor and Wilson in the January 1941 issue of the Journal of the Society of Dyers and Colourists, page 6. Further details for the preparation of these compounds are given by the same authors in reference 3 of this article (same Journal, 1939, 55, 450). An example of the procedure employed in the preparation is as follows:

Thiophene-2-carb0xyl-4-clzlorobenzanilide Equimolar quantities of 2-thiophene carboxylic acid and p-chloroaniline are heated to 70 C. Then, 6 cc. of phosphorus trichloride are added over a period of 30 minutes while the whole is well stirred. The mixture is next heated, with frequent stirring, in an oil bath at 115 C. for four hours. The viscous mass thus produced is cooled, mixed with alcohol and reheated to dissolve. On cooling and leaving overnight, a brown solid separates, a further quantity of which is obtained by diluting the mother liquid with water. Total yield of thiophene-Z- carboxyl-4-chlorobenzanilide is about 85-90%, and the material may be recrystallized from benzene-nitrobenzene (1:1).

The compounds of the present invention have been found to have a strong germicidal effect upon microorganisms, such as bacteria, fungi, and the like. Table I lists a number of compounds prepared in accordance with the present invention, and gives their germicidal efiectiveness against S. aureus in agar test plates, as millimeters of zone of inhibition. The tests were carred out in triplicate as follows:

Bacteriological tests were performed against Staphylococcus aureus with a 24-hour culture at 37 C. Each of the compounds in Table I was incorporated in soap of Ivory brand (a neutral white high grade toilet soap consisting of a mixture of 80% sodium soap and 20% potassium soap produced from a 70% tallow and 30% coconut oil glyceride blend, in accordance With US. Patent 2,295,594), in 1% by weight concentration of soap and 0.1% of the compound listed. Cotton disks of 10 mm. diameter were steeped in this mixture, thoroughly rinsed, dried, and applied to seeded agar in Petri dishes, and the zones of inhibition were read after 24 hours, the average data being reported in Table I.

These compounds of the present invention are useful -gums, and the like, and mixtures thereof.

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in compositions comprising a germicidally inert material, i.e., relatively speaking. For example, some soaps and detergents possess a bactericidal action, but such action, relative to those of the compounds of the present invention, is weak and activity of the composition. In such compositions, the compounds of the present invention may be employed in concentrations as low as 10 p.p.m., although, from a practical point of view, it is desirable to use as much as 50 ppm. or 0.001% by weight, or 0.01%, and as much as 0.1%, or more. The term germicidal activity includes inhibiting and killing action against bacteria, fungi and similar organisms.

Partcularly useful compositions of the present invention are those comprising soaps and detergents, and especially toilet soaps or cosmetic detergents in which the compounds of the present invention may be employed in concentrations of 0.1% to 0.5% by weight, or even as much as 1% or more. The term detergent employed herein will be used to include all synthetic and natural cleansing compositions, including cationic detergents, such as dimethyl stearamido-propyl-2-hydroxy-ammoniurn dihy-drogen phosphate, anionic detergents such as commercial soaps, e.g., alkali metal soaps of hydrolyzed natural or synthetic glycerides of fatty and similar organic acids, e.g., sodium and potassium stearates or oleates, ampholytic detergents, such as sarcosine, nonionic detergent such as polyoxypropylene polyoxyethylene condensates, natural detergents, such as starches, vegetable The term soap employed herein is used in its popular or ordinary meaning, i.e., a cleansing composition prepared from an alkali metal compound such as potassium or sodium hydroxide and a fat or fatty acid, both saturated and unsaturated.

One valuable use of the compounds of the present invention is the use thereof to sanitize fibrous material such as cotton gauze, dressings, textiles, paper pulp, and the like. They also serve as antiseptic agents when incorporated in plastic or rubber compositions, prior to molding into articles of commerce, such as baby rattles, gloves, food Wrappers and the like.

TABLE I Compound Zone of N0. Formula Inhibition,

S H l 1 H S II I 2 N I 2.0

01 s u 3 l I 01 Cl 0 H I l S H l 4 Br- HO-N 3,0

s H H S H I 5 o1 W-C-N- 1 a TABLE ICntinued Compound Zone of N0. Formula Inhibition,

i S o Br CN@Br 3.0

I I Br Br Br II I I S 7 137 \,CN--Br 3.0

Br Br i i S s CN 4.0

I! l I S II I 9 H NCN- 4.5

A study of Table I Will reveal that the germicidal potency of the compounds of the present invention do not appear to be increased substantially by the addition of extra halogen atoms to the nuclei. This is apparent when Compound No. 3 is compared with No. 4. It therefore appears that the high germicidal power of the compounds of the present invention is inherent in the structural arrangement of the molecules, rather than to the halogen su-bstituents.

4 I claim: 1. A compound having the general formula:

wherein 2. A compound, according to claim 1, having the formula:

3 iii 3. A compound, according to claim 1, having the formula:

No references cited.

JOHN D. RANDOLPH, Primary Examiner.

r C. SHURKO, Assistant Examiner. 

1. A COMPOUND HAIVNG THE GENERAL FORMULA: 